In Vivo Structures of the Helicobacter pylori cag Type IV Secretion System
Abstract
The type IV secretion system (T4SS) is a versatile nanomachine that translocates diverse effector molecules between microbes and into eukaryotic cells. Here, using electron cryotomography, we reveal the molecular architecture of the Helicobacter pylori cag T4SS. Although most components are unique to H. pylori, the cag T4SS exhibits remarkable architectural similarity to other T4SSs. Our images revealed that, when H. pylori encounters host cells, the bacterium elaborates membranous tubes perforated by lateral ports. Sub-tomogram averaging of the cag T4SS machinery revealed periplasmic densities associated with the outer membrane, a central stalk, and peripheral wing-like densities. Additionally, we resolved pilus-like rod structures extending from the cag T4SS into the inner membrane, as well as densities within the cytoplasmic apparatus corresponding to a short central barrel surrounded by four longer barrels. Collectively, these studies reveal the structure of a dynamic molecular machine that evolved to function in the human gastric niche.
Additional Information
© 2018 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Received 16 October 2017, Revised 16 January 2018, Accepted 19 March 2018, Available online 17 April 2018. We thank Dr. Tim Cover for providing H. pylori strains and Dr. Joseph Vogel and Dr. Maria Hadjifrangiskou for helpful discussions. This work was supported by NIH grant R01 AI127401 to G.J.J., NIH grant F32 DK105720 to C.L.S., NIH grant T32 A1007474 to C.L.S., and the Burroughs Wellcome Fund 2016 Collaborative Research Travel Grant1016383 to C.L.S. Author Contributions: Y.-W.C., C.L.S., and L.A.R. prepared the samples. Y.-W.C. collected and processed the electron cryotomography data and generated the sub-tomogram averages. All authors analyzed and interpreted the electron cryotomography data. G.J.J. supervised the project. Y.-W.C., C.L.S., and G.J.J. wrote the paper, with input from all authors. Data and Software Availability: The accession numbers for the sub-tomogram averages of cag T4SS machinery that support the findings of this study are EMDB: 7474 (aligned on the periplasmic region) and EMDB: 7475 (aligned on the cytoplasmic region). The authors declare no competing interests.Attached Files
Published - 1-s2.0-S2211124718304467-main.pdf
Accepted Version - nihms962086.pdf
Submitted - 195685.full.pdf
Supplemental Material - mmc1.pdf
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Additional details
- PMCID
- PMC5931392
- Eprint ID
- 85906
- Resolver ID
- CaltechAUTHORS:20180417-152641769
- R01 AI127401
- NIH
- F32 DK105720
- NIH Postdoctoral Fellowship
- T32 A1007474
- NIH Predoctoral Fellowship
- 1016383
- Burroughs Wellcome Fund
- Created
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2018-04-17Created from EPrint's datestamp field
- Updated
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2022-03-11Created from EPrint's last_modified field